Arimoclomol in Amyotropic Lateral Sclerosis - Open Label Extension Trial
- Registration Number
- NCT03836716
- Lead Sponsor
- ZevraDenmark
- Brief Summary
A multicenter, non-randomized, open label trial, to assess long term safety and efficacy of Arimoclomol in subjects with Amyotrophic Lateral Sclerosis (ALS) who have completed the ORARIALS-01 trial.
- Detailed Description
The planned duration of the open-label trial was 152 weeks, but the trial was terminated early as a consequence of the results of ORARIALS-01 which did not meet any of its efficacy endpoints. Therefore, the actual mean duration of open-label treatment was approximately 28 weeks (range approximately 2 to 71 weeks).
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 120
- Subject is able to comprehend and is willing to provide written informed consent and is capable and willing to comply with trial procedures, or in the circumstance that the subject is incompetent, informed consent/assent is provided in accordance with local regulation and/or procedures
- Subject has completed the ORARIALS-01 trial (i.e., met one of the surrogate survival endpoints of tracheostomy or PAV or has completed the 76 weeks randomized treatment period)
- Subject completed ORARIALS-01 while on treatment, where on treatment is defined as having taken the last dose of IMP within 2 weeks of the End of Trial visit (whether at week 76 or prior)
-
Known or suspected allergy or intolerance to the IMP (Arimoclomol or constituents)
-
Exposure to any other investigational treatment, advanced therapy medicinal product or use of any other prohibited concomitant medications
-
Women who are lactating or pregnant, or men or women unwilling to use a highly effective method of birth control if not surgically sterile (defined as bilateral tubal ligation, bilateral oophorectomy, or hysterectomy for women; vasectomy for men) for female participants until 4 weeks after last dose and for male participants until 3 months after last dose. Pre-menopausal women must have a negative pregnancy test prior to dosing with trial medication.
-
Any of the following medically significant conditions:
- Clinically significant renal or hepatic disease OR clinical laboratory assessment (results ≥ 3 times the upper limit of normal [ULN] for aspartate aminotransferase and/or alanine aminotransferase, bilirubin ≥ 2 times the ULN, or creatinine ≥ 1.5 times the ULN).
- Any new condition or worsening of existing condition which, in the opinion of the investigator, would put the subject at undue risk.
-
Any serious adverse event or moderate/severe adverse event from the ORARIALS-01 trial which is ongoing at the time of transitioning to ORARIALS-02 and assessed as probably related to IMP
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arimoclomol Arimoclomol 248 mg arimoclomol base (equivalent to 400 mg arimoclomol citrate) 3 times daily
- Primary Outcome Measures
Name Time Method Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (1) Week 76 Standard clinical chemistry parameters. Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase.
Mean and Change From Baseline in Vital Signs - Blood Pressure Week 76 Standard vital signs. Systolic and diastolic blood pressure.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (2) Week 76 Standard hematology parameters. Percentage of leukocytes were determined for basophils, eosinophils, lymphocytes, monocytes, and neutrophils
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematocrit Week 76 Standard hematology parameter.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Albumin and Protein Week 76 Standard clinical chemistry parameters.
Mean and Change From Baseline in Vital Signs - Temperature Week 76 Standard vital signs measurement.
Columbia-Suicide Severity Rating Scale (C-SSRS) Over the Open-label Treatment Period From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks The C-SSRS is a detailed questionnaire assessing both suicidal behavior and suicidal ideation through a series of simple, plain-language questions administered as an interview by a qualified investigator or delegate.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Open-label Treatment Period From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks Adverse event (AE) data were collected throughout the trial until early termination. The average duration of exposure was 198.7 days (approximately 28 weeks; standard deviation 99.57 days; minimum 16 days, maximum 494 days). 58 participants (48.3%) were exposed less than 6 months; 55 participants (45.8%) were exposed 6 to less than 12 months; 7 participants (5.8%) were exposed 12 to less than 18 months. No participant was treated for 76 weeks.
Participants with on-treatment TEAEs are reported. An on-treatment TEAE is any TEAE in the on-treatment period defined as the time from first dose of IMP until 14 days since the last preceding administration of IMP (either before a temporary IMP interruption with duration \>14 days or the last dose at the end of trial). A participant may have several on-treatment periods separated by interruption intervals.Mean and Change From Baseline in Clinical Safety Laboratory Tests - Erythrocytes Week 76 Standard hematology parameter.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Cystatin C Week 76 Standard clinical chemistry parameter.
Mean and Change From Baseline in Vital Signs - Respiratory Rate Week 76 Standard vital signs measurement.
Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Safety Laboratory Tests and Vital Signs Over the Open-label Treatment Period From Day 1 in ORARIALS-02 to Early Termination, an average of approximately 28 weeks Clinical safety laboratory data and vital signs were collected throughout the trial until early termination. The average duration of exposure was 198.7 days (approximately 28 weeks; standard deviation 99.57 days; minimum 16 days, maximum 494 days). 58 participants (48.3%) were exposed less than 6 months; 55 participants (45.8%) were exposed 6 to less than 12 months; 7 participants (5.8%) were exposed 12 to less than 18 months. No patient was treated for 76 weeks.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (3) Week 76 Standard clinical chemistry parameters. Bilirubin, Creatinine, Direct Bilirubin, and Indirect Bilirubin.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hematology (1) Week 76 Standard hematology parameters. White blood cell differential count for basophils, eosinophils, leukocytes, lymphocytes, monocytes, and neutrophils, and platelet count.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Hemoglobin Week 76 Standard hematology parameter.
Mean and Change From Baseline in Clinical Safety Laboratory Tests - Clinical Chemistry (2) Week 76 Standard clinical chemistry parameters. Calcium, Calcium Corrected, Cholesterol, Glucose, HDL Cholesterol, LDL Cholesterol, Potassium, Sodium, Triglycerides, and Urea Nitrogen.
Mean and Change From Baseline in Vital Signs - Pulse Rate Week 76 Standard vital signs measurement.
- Secondary Outcome Measures
Name Time Method Change in ALS Functional Rating Scale - Revised (ALSFRS-R) From Baseline to Week 76 Week 76 The ALSFRS-R is an ordinal rating scale used to determine subjects' subjective assessment of their capability and independence with 12 functional activities ('speech', 'salivation', 'swallowing', handwriting', 'cutting food and handling utensils', 'dressing and hygiene', 'turning in bed and adjusting bed clothes', 'walking', 'dyspnoea', 'orthopnoea' and 'respiratory insufficiency'). Each activity is rated on a 5-point scale (from 0 \[no ability\] to 4 \[normal\]), giving a maximal ALSFRS-R score of 48. A lower score corresponds to a lower capability and independence.
Change in Percentage (%) Predicted Slow Vital Capacity (SVC) From Baseline to Week 76 (for Subjects Who Did Not Meet the Survival Endpoint in the ORARIALS-01 Trial) 76 weeks Slow vital capacity (SVC) measures the volume that can be exhaled from a full inhalation after exhaling to a maximum as slowly as possible. Predicted SVC was derived per European Community of Coal and Steel (ECCS) reference equations:
* If male: Predicted SVC = 0.061 x height (cm) - 0.028 x age (years) - 4.65
* If female: Predicted SVC = 0.0466 x height (cm) - 0.024 x age (years) - 3.28
Trial Locations
- Locations (23)
University of Pensylvania, Perelman Center for Advanced Medicine - Penn Neuroscience Center
🇺🇸Philadelphia, Pennsylvania, United States
Hospital Universitario Vall d'Hebron ALS Unit. Consultas Externas; Office: 9-10-11
🇪🇸Barcelona, Spain
Leonard Wolfson Experimental Neurology Centre
🇬🇧London, United Kingdom
Providence Brain & Spine Institute
🇺🇸Portland, Oregon, United States
University of Miami
🇺🇸Miami, Florida, United States
Universitaetsklinikum Ulm - Klinik fuer Neurologie
🇩🇪Ulm, Germany
St. Joseph's Hospital and Medical Center (SJHMC) - Barrow Neurological Institute (BNI) - The Gregory W. Fulton ALS and Neuromuscular Disease Center
🇺🇸Phoenix, Arizona, United States
Medizinische Hochschule Hannover (MHH) - Klinik fuer Neurologie
🇩🇪Hannover, Germany
Citi Clinic
🇵🇱Warsaw, Poland
Hospital for Special Surgery
🇺🇸New York, New York, United States
UC Irvine Health ALS and Neuromuscular Center
🇺🇸Orange, California, United States
Catholic University Leuven
🇧🇪Leuven, Belgium
University of Virginia Health System
🇺🇸Charlottesville, Virginia, United States
Centre Hospitalier Regional Universitaire (CHRU) Montpellier - Hopital Gui De Chauliac
🇫🇷Montpellier, France
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Groupe Hospitalier Pitie-Salpetriere - Centre d'Investigation Clinique Neurosciences 1422
🇫🇷Paris, France
Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum (CVK) - Ambulanz fuer ALS und andere Motoneuronenerkrankungen
🇩🇪Berlin, Germany
Instituti Clinica Scientifici Maugeri
🇮🇹Milano, Italy
Azienda Ospedaliero Universitaria (AUO) di Torino - Citta'della Salute e della Scienza di Torino
🇮🇹Torino, Italy
Centrum Medyczne NeuroProtect
🇵🇱Warsaw, Poland
Hospital Carlos III - Hospital Universitario La Paz, ALS Unit
🇪🇸Madrid, Spain
Umeå University Hospital
🇸🇪Umeå, Sweden
University Medical Center Utrecht
🇳🇱Utrecht, Netherlands